Macromolecular prodrugs of aspirin with HPMC: A nano particulate drug design, characterization, and pharmacokinetic studies View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2011-11-03

AUTHORS

Muhammad Ajaz Hussain, Khawar Abbas, Muhammad Sher, Muhammad Nawaz Tahir, Wolfgang Tremel, Mohammad Saeed Iqbal, Muhammad Amin, Munair Badshah

ABSTRACT

This article presents the synthesis of novel hydroxypropylmethylcellulose (HPMC)-aspirin (ASP) conjugates, i.e. macromolecular prodrugs, through the reaction of HPMC with ASP after its in situ activation by 4-methylbenzenesulfonyl chloride. The highly pure ASP prodrugs obtained by this homogeneous and elegant esterification method were characterized using different spectroscopic and chromatographic techniques. Nanoparticulate drug design was successfully achieved by the conversion of free hydroxyls of the polymer into acetates. Transmission electron microscopy and scanning electron microscopy showed nanoparticle formation with the major population size distribution of around 450 nm. Nevertheless, the pharmacokinetics of the HPMC conjugates were studied using high performance liquid chromatography. The pharmacokinetic data indicated that a single dose of 132.6 mg of HPMC-ASP was well tolerated in animal studies without any adverse effects. The maximum plasma concentration (Cmax) of HPMC-ASP was found to be 14.6 μg·L−1 with a tmax of 1 h. The plasma half-life and clearance and the volume of HPMC-ASP distribution were 4.6 h, 3.23 L·h−1, and 21.8 L·kg−1, respectively. The elimination of HPMC-ASP followed first-order kinetics with r2 of 0.9643. The results presented in this paper show the great potential of HPMCASP as a more effective, safe, and stable prodrug. More... »

PAGES

1296-1302

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s13233-011-1212-2

DOI

http://dx.doi.org/10.1007/s13233-011-1212-2

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https://app.dimensions.ai/details/publication/pub.1003421322


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